Platelet-activating factor mediates monocyte chemoattractant protein-1 expression in glomerular immune injury.
These studies were designed to determine the possible role of platelet-activating factor (PAF) in the production of monocyte chemoattractant protein-1 (MCP-1) in glomerular immune injury. The glomerular lesion was induced in isolated perfused rat kidneys by a rabbit anti-rat-thymocyte serum (ATS) and rat serum (RS) as a complement source. Perfusion of kidneys with ATS and RS results in the selective binding of the antiserum to the glomerular mesangium with consecutive intraglomerular activation of complement. Antibody binding and complement activation induced a significant increase in glomerular MCP-1 mRNA levels when assessed by Northern blotting or RT-PCR. Decomplemented RS or non antibody rabbit IgG had only moderate effects on glomerular MCP-1 mRNA levels. The PAF receptor antagonist WEB 2170 almost completely blocked the ATS and RS induced MCP-1 mRNA levels. Perfusion of control kidneys with PAF increased MCP-1 mRNA expression, an effect which was blocked by WEB 2170. Glomerular MCP-1 protein formation, assessed by Western blotting, was stimulated following ATS and RS and PAF, respectively, was blocked by WEB 2170. These data show that PAF, derived from glomerular resident cells following antibody and complement induced injury, stimulates MCP-1 expression. In addition to the direct effects on leukocyte adhesion and activation PAF may mediate inflammatory cell influx in glomerular injuries due to the release of MCP-1.
Jocks
T
T
Department of Medicine, University of Hamburg, Germany.
Freudenberg
J
J
Zahner
G
G
Stahl
R A
RA
D000818:Animals; D001381:Azepines / Q000494:pharmacology; D018932:Chemokine CCL2 / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D003165:Complement System Proteins / Q000276:immunology*; D005921:Glomerulonephritis / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000378:metabolism*; D008297:Male; D010972:Platelet Activating Factor / Q000502:physiology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D014230:Triazoles / Q000494:pharmacology
D001381:Azepines; D018932:Chemokine CCL2; D010972:Platelet Activating Factor; D012333:RNA, Messenger; D014230:Triazoles; D003165:Complement System Proteins; C063964:bepafant